Although the mechanism underlying coronary conduit artery spasm in vasospastic angina (VAP) remains unknown, coronary endothelial dysfunction has been suggested as playing an important role. However, it remains unknown whether this endothelium-mediated abnormal vasomotion is uniformly evident irrespective of site of vascular bed or vessel size. Plethysmographic studies were carried out to measure changes in forearm resistance vessel blood flow (FBF) induced by acetylcholine (Ach), sodium nitroprusside, and 10-min occlusion-induced reactive hyperemia in 12 patients with VAP, 14 patients with atherosclerotic (>75% fixed stenosis) coronary artery disease (CAD), and 16 healthy controls. FBF responses induced by the endothelium-dependent vasodilator Ach were significantly augmented in patients with VAP compared to controls, whereas this type of FBF response in patients with CAD was significantly blunted (at the maximum dose: VAP, 24.1 +/- 3.0; controls, 17.2 +/- 1.9; CAD, 12.8 +/- 1.9 ml/min per 100 ml; p < 0.01). However, there were no significant differences in FBF responses during infusion of sodium nitroprusside among the three subject groups. Reactive hyperemic FBF which represents maximum vasodilatory capacity did not differ among the three. To assess the role of nitric oxide in the augmented endothelium-dependent response in VAP, Ach-induced FBF response was determined before and after administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine in another VAP group (n = 7). After nitric oxide synthase inhibition, the peak FBF response induced by Ach decreased from 23.3 +/- 3.2 to 14.1 +/- 1.6 ml/min per 100 ml (p < 0.05). In conclusion, the above data suggest that endothelium-dependent vasomotor response to Ach in limb resistance vessels is augmented in patients with vasospastic angina. It seems unlikely that endothelial function is consistently depressed in any area of the vascular bed in this disorder.